← Back
Diagnosis and tests

BCR::ABL1 and the Philadelphia chromosome

The related article (“CML: symptoms, phases and diagnosis”) explains bone marrow aspiration. This topic looks closely at the best-known genetic change searched for in that sample: the Philadelphia chromosome and the BCR::ABL1 fusion gene.

Last updated: ~1 min read
Two chromosomes exchanging ends.
Figure 1.Chromosomes 9 and 22 swap ends.

01Short answer

The Philadelphia chromosome is a shortened chromosome 22 that results from an exchange of pieces between chromosomes 9 and 22, the t(9;22) translocation. In this exchange, the ABL1 gene from chromosome 9 joins the BCR gene on chromosome 22, creating a new fusion gene, BCR::ABL1. This gene makes a tyrosine kinase protein that stays permanently “switched on” and constantly signals the cell to divide. BCR::ABL1 is found in almost all cases of CML, in a large share of adults with ALL and rarely in AML. It is detected by karyotype, FISH and PCR. Most importantly, this protein is the target of drugs called tyrosine kinase inhibitors (TKIs), and PCR makes it possible to follow the response to treatment.

02Simple explanation

t(9;22): the Philadelphia chromosome.

BCR::ABL1: the fusion gene.

A target for TKIs.

03Scientific explanation

Transcript types: CML usually has the p210 form (e13a2/e14a2), while Ph+ ALL often has p190 (e1a2); this affects which PCR is used for monitoring.

Resistance mutations: mutations in the ABL1 kinase domain can reduce the response to TKIs and are tested for in that situation.

04What happens in the body?

The swap

Chromosomes 9 and 22 exchange their ends.

A short chromosome

The shortened chromosome 22 was first described in Philadelphia.

A short chromosome among normal ones.
Figure 2.The shortened Philadelphia chromosome.

A stuck switch

The BCR::ABL1 protein is like a switch stuck “on”, sending signals all the time.

A glowing switch stuck on.
Figure 3.A switch stuck “on”.

05How BCR::ABL1 forms

Four steps.

Two chromosomes — 9 and 22.1Two chromosomes9 and 22.
Breaks — The ends break off.2BreaksThe ends break off.
Swap — Pieces change places.3SwapPieces change places.
Fusion — An always-on kinase.4FusionAn always-on kinase.

06Where BCR::ABL1 is found

DiseaseApproximate frequency
CMLAlmost always
ALL in adultsA large share, rising with age
ALL in childrenA small share
AMLRare

07Key terms

Philadelphia chromosome
The shortened chromosome 22 after t(9;22).
BCR::ABL1
The fusion gene.
Tyrosine kinase
An enzyme that passes on cell signals.
TKI
Tyrosine kinase inhibitor.
Transcript
An RNA copy made from a gene.

08Key points

  • The Philadelphia chromosome comes from t(9;22).
  • BCR::ABL1 is a fusion gene.
  • It makes an always-on kinase.
  • It is almost always present in CML.
  • TKI drugs target it.
  • PCR follows the response.

09Frequently asked questions

Is it inherited?

No; it arises only in the leukaemia cells.

Are Ph+ ALL and CML the same disease?

No; the same gene change occurs in different diseases (“What the Philadelphia chromosome means”).

How soon is the result ready?

FISH and PCR in a few days, the karyotype later.

10Questions for your doctor

Take these questions to your appointment. The ones you save are collected on the “My questions” page and stay on this device only.

  1. Is it inherited?

  2. Are Ph+ ALL and CML the same disease?

  3. How soon is the result ready?

My questions

12Sources

  1. National Cancer Institute (NCI). Definition: Philadelphia chromosome
  2. MedlinePlus Genetics. BCR gene
  3. National Cancer Institute (NCI). CML treatment (PDQ), patient version
  4. MedlinePlus Genetics (U.S. National Library of Medicine). What is a gene variant and how do variants occur?
  5. Macmillan Cancer Support. Bone marrow biopsy
  6. National Cancer Institute (NCI). NCI Dictionary of Cancer Terms: flow cytometry
  7. National Cancer Institute (NCI). NCI Dictionary of Cancer Terms: FISH
  8. National Cancer Institute (NCI). NCI Dictionary of Cancer Terms: next-generation sequencing
  9. MedlinePlus (U.S. National Library of Medicine). BCR-ABL1 Genetic Test
  10. Leukemia, 2020. European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia
Medical disclaimerThis information is for educational purposes only and does not replace medical advice.
Last updated: ← Back to the list

Open the interactive site →